Assessment of population infection with SARS-CoV-2 in Ontario,Canada, March to June 2020

BackgroundSerosurveys for SARS-CoV-2 aim to estimate the proportion of the population that has been infected.AimThis observational study assesses the seroprevalence of SARS-CoV-2 antibodies in Ontario, Canada during the first pandemic wave.MethodsUsing an orthogonal approach, we tested 8,902 residual specimens from the Public Health Ontario laboratory over three time periods during March–June 2020 and stratified results by age group, sex and region. We adjusted for antibody test sensitivity/specificity and compared with reported PCR-confirmed COVID-19 cases.ResultsAdjusted seroprevalence was 0.5% (95% confidence interval (CI): 0.1–1.5) from 27 March–30 April, 1.5% (95% CI: 0.7–2.2) from 26–31 May, and 1.1% (95% CI: 0.8–1.3) from 5–30 June 2020. Adjusted estimates were highest in individuals aged ≥ 60 years in March–April (1.3%; 95% CI: 0.2–4.6), in those aged 20–59 years in May (2.1%; 95% CI: 0.8–3.4) and in those aged ≥ 60 years in June (1.6%; 95% CI: 1.1–2.1). Regional seroprevalence varied, and was highest for Toronto in March–April (0.9%; 95% CI: 0.1–3.1), for Toronto in May (3.2%; 95% CI: 1.0–5.3) and for Toronto (1.5%; 95% CI: 0.9–2.1) and Central East in June (1.5%; 95% CI: 1.0–2.0). We estimate that COVID-19 cases detected by PCR in Ontario underestimated SARS-CoV-2 infections by a factor of 4.9.ConclusionsOur results indicate low population seroprevalence in Ontario, suggesting that public health measures were effective at limiting the spread of SARS-CoV-2 during the first pandemic wave.     

Association between SARS-CoV-2 infection and Kawasaki-like multisystem inflammatory syndrome: a retrospective matched case–control study,Paris, France,April to May 2020

We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Kawasaki disease (KD)-like multisystem inflammatory syndrome in a retrospective case–control study in France. RT-PCR and serological tests revealed SARS-CoV-2 infection in 17/23 cases vs 11/102 controls (matched odds ratio: 26.4; 95% confidence interval: 6.0–116.9), indicating strong association between SARS-CoV-2 infection and KD-like illness. Clinicians should keep a high level of suspicion for KD-like illness during the COVID-19 pandemic.     

Impact of the Omicron variant on SARS-CoV-2 reinfections in France,March 2021 to February 2022

Since the first reports in summer 2020, SARS-CoV-2 reinfections have raised concerns about the immunogenicity of the virus, which will affect SARS-CoV-2 epidemiology and possibly the burden of COVID-19 on our societies in the future. This study provides data on the frequency and characteristics of possible reinfections, using the French national COVID-19 testing database. The Omicron variant had a large impact on the frequency of possible reinfections in France, which represented 3.8% of all confirmed COVID-19 cases since December 2021.     

Nationwide study on SARS-CoV-2 transmission within households from lockdown to reopening,Denmark, 27 February 2020 to 1 August 2020

BackgroundThe COVID-19 pandemic is one of the most serious global public health threats of recent times. Understanding SARS-CoV-2 transmission is key for outbreak response and to take action against the spread of disease. Transmission within the household is a concern, especially because infection control is difficult to apply within this setting.AimThe objective of this observational study was to investigate SARS-CoV-2 transmission in Danish households during the early stages of the COVID-19 pandemic.MethodsWe used comprehensive administrative register data from Denmark, comprising the full population and all COVID-19 tests from 27 February 2020 to 1 August 2020, to estimate household transmission risk and attack rate.ResultsWe found that the day after receiving a positive test result within the household, 35% (788/2,226) of potential secondary cases were tested and 13% (98/779) of these were positive. In 6,782 households, we found that 82% (1,827/2,226) of potential secondary cases were tested within 14 days and 17% (371/2,226) tested positive as secondary cases, implying an attack rate of 17%. We found an approximate linear increasing relationship between age and attack rate. We investigated the transmission risk from primary cases by age, and found an increasing risk with age of primary cases for adults (aged ≥ 15 years), while the risk seems to decrease with age for children (aged < 15 years).ConclusionsAlthough there is an increasing attack rate and transmission risk of SARS-CoV-2 with age, children are also able to transmit SARS-CoV-2 within the household.     

Side-By-Side Evaluation of Three Commercial ELISAs for the Quantification of SARS-CoV-2 IgG Antibodies

In December 2020, WHO presented the first international standard (WHO IS) for anti-SARS-CoV-2 immunoglobulin. This standard is intended to serve as a reference reagent against which serological tests can be calibrated, thus creating better comparability of results between different tests, laboratories, etc. Here, we have examined three different commercial ELISA kits for the quantification of SARS-CoV-2 IgG antibodies, namely the Anti-SARS-CoV-2 QuantiVac ELISA (IgG) (Euroimmun, Lübeck, Germany), the SERION ELISA agile (Institut Virion Serion, Würzburg, Germany), and the COVID-19 quantitative IgG ELISA (DeMediTec Diagnostics, Kiel, Germany). According to the manufacturers, all are calibrated against the WHO IS and can provide results in either international units (IU) (DeMediTec) or arbitrary antibody units (BAU) per milliliter (Euroimmun, Virion Serion), which are numerically identical, according to the WHO. A total of 50 serum samples from vaccinated individuals were tested side by side and according to the manufacturer’s instructions. We compared the test results of all three assays with each other to assess comparability and with a quantitative in-house virus neutralization test (micro-NT). In summary, our data are consistent with other studies published on this topic that tested similar assays from different manufacturers. Overall, the agreement between quantitative ELISAs is variable and cannot be used interchangeably despite calibration against a standard. Therefore, interpretation of results must still be individualized and tailored to each case. More importantly, our results highlight that quantitative ELISAs in their current form cannot replace neutralization tests.     

SARS-CoV-2 infection in schools in a northern French city: a retrospective serological cohort study in an area of high transmission,France, January to April 2020

BackgroundChildren’s role in SARS-CoV-2 epidemiology remains unclear. We investigated an initially unnoticed SARS-CoV-2 outbreak linked to schools in northern France, beginning as early as mid-January 2020.AimsThis retrospective observational study documents the extent of SARS-CoV-2 transmission, linked to an affected high school (n = 664 participants) and primary schools (n = 1,340 study participants), in the context of unsuspected SARS-CoV-2 circulation and limited control measures.MethodsBetween 30 March and 30 April 2020, all school staff, as well as pupils and their parents and relatives were invited for SARS-CoV-2 antibody testing and to complete a questionnaire covering symptom history since 13 January 2020.ResultsIn the high school, infection attack rates were 38.1% (91/239), 43.4% (23/53), and 59.3% (16/27), in pupils, teachers, and non-teaching staff respectively vs 10.1% (23/228) and 12.0% (14/117) in the pupils’ parents and relatives (p < 0.001). Among the six primary schools, three children attending separate schools at the outbreak start, while symptomatic, might have introduced SARS-CoV-2 there, but symptomatic secondary cases related to them could not be definitely identified. In the primary schools overall, antibody prevalence in pupils sharing classes with symptomatic cases was higher than in pupils from other classes: 15/65 (23.1%) vs 30/445 (6.7%) (p < 0.001). Among 46 SARS-CoV-2 seropositive pupils < 12 years old, 20 were asymptomatic. Whether past HKU1 and OC43 seasonal coronavirus infection protected against SARS-CoV-2 infection in 6–11 year olds could not be inferred.ConclusionsViral circulation can occur in high and primary schools so keeping them open requires consideration of appropriate control measures and enhanced surveillance.     

Determining the communicable period of SARS-CoV-2: A rapid review of the literature,March to September 2020

IntroductionStandard testing for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is based on RT-PCR tests, but detection of viral genetic material alone does not indicate ongoing infectious potential. The ability to isolate whole virus represents a better proxy for infectivity.AimThe objective of this study was to gain an understanding of the current literature and compare the reported periods of positive SARS-CoV-2 detection from studies that conducted RT-PCR testing in addition to experiments isolating whole virus.MethodsUsing a rapid review approach, studies reporting empirical data on the duration of positive RT-PCR results and/or successful viral isolation following SARS-CoV-2 infection in humans were identified through searches of peer-reviewed and pre-print health sciences literature. Articles were screened for relevance, then data were extracted, analysed, and synthesised.ResultsOf the 160 studies included for qualitative analysis, 84% (n = 135) investigated duration of positive RT-PCR tests only, 5% (n = 8) investigated duration of successful viral isolations, while 11% (n = 17) included measurements on both. There was significant heterogeneity in reported data. There was a prolonged time to viral clearance when deduced from RT-PCR tests compared with viral isolations (median: 26 vs 9 days).DiscussionFindings from this review support a minimum 10-day period of isolation but certain cases where virus was isolated after 10 days were identified. Given the extended time to viral clearance from RT-PCR tests, future research should ensure standard reporting of RT-PCR protocols and results to help inform testing policies aimed at clearance from isolation.     

Epidemiological and clinical insights from SARS-CoV-2 RT-PCR crossing threshold values,France, January to November 2020

BackgroundThe COVID-19 pandemic has led to an unprecedented daily use of RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of quantification cycles (Cq), is debated because of strong potential biases.AimWe explored the possibility to use Cq values from SARS-CoV-2 screening tests to better understand the spread of an epidemic and to better understand the biology of the infection.MethodsWe used linear regression models to analyse a large database of 793,479 Cq values from tests performed on more than 2 million samples between 21 January and 30 November 2020, i.e. the first two pandemic waves. We performed time series analysis using autoregressive integrated moving average (ARIMA) models to estimate whether Cq data information improves short-term predictions of epidemiological dynamics.ResultsAlthough we found that the Cq values varied depending on the testing laboratory or the assay used, we detected strong significant trends associated with patient age, number of days after symptoms onset or the state of the epidemic (the temporal reproduction number) at the time of the test. Furthermore, knowing the quartiles of the Cq distribution greatly reduced the error in predicting the temporal reproduction number of the COVID-19 epidemic.ConclusionOur results suggest that Cq values of screening tests performed in the general population generate testable hypotheses and help improve short-term predictions for epidemic surveillance.     

Prior infection by seasonal coronaviruses,as assessed by serology,does not prevent SARS-CoV-2 infection and disease in children,France, April to June 2020

BackgroundChildren have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections.AimWe tested if prior infections by seasonal coronaviruses (HCoV) NL63, HKU1, 229E or OC43 as assessed by serology, provide cross-protective immunity against SARS-CoV-2 infection.MethodsWe set a cross-sectional observational multicentric study in pauci- or asymptomatic children hospitalised in Paris during the first wave for reasons other than COVID (hospitalised children (HOS), n = 739) plus children presenting with MIS (n = 36). SARS-CoV-2 antibodies directed against the nucleoprotein (N) and S1 and S2 domains of the spike (S) proteins were monitored by an in-house luciferase immunoprecipitation system assay. We randomly selected 69 SARS-CoV-2-seropositive patients (including 15 with MIS) and 115 matched SARS-CoV-2-seronegative patients (controls (CTL)). We measured antibodies against SARS-CoV-2 and HCoV as evidence for prior corresponding infections and assessed if SARS-CoV-2 prevalence of infection and levels of antibody responses were shaped by prior seasonal coronavirus infections.ResultsPrevalence of HCoV infections were similar in HOS, MIS and CTL groups. Antibody levels against HCoV were not significantly different in the three groups and were not related to the level of SARS-CoV-2 antibodies in the HOS and MIS groups. SARS-CoV-2 antibody profiles were different between HOS and MIS children.ConclusionPrior infection by seasonal coronaviruses, as assessed by serology, does not interfere with SARS-CoV-2 infection and related MIS in children.     

Occupation- and age-associated risk of SARS-CoV-2 test positivity,the Netherlands,June to October 2020

High coronavirus incidence has prompted the Netherlands to implement a second lockdown. To elucidate the epidemic’s development preceding this second wave, we analysed weekly test positivity in public test locations by population subgroup between 1 June and 17 October 2020. Hospitality and public transport workers, driving instructors, hairdressers and aestheticians had higher test positivity compared with a reference group of individuals without a close-contact occupation. Workers in childcare, education and healthcare showed lower test positivity.     

Under-diagnosis of SARS-CoV-2 infections among children aged 0–15 years,a nationwide seroprevalence study,Israel, January 2020 to March 2021

Until recently, children and adolescents were not eligible for COVID-19 vaccination. They may have been a considerable source of SARS-CoV-2 spread. We evaluated SARS-CoV-2 IgG antibody seroprevalence in Israeli children aged 0–15 years from January 2020 to March 2021. Seropositivity was 1.8–5.5 times higher than COVID-19 incidence rates based on PCR testing. We found that SARS-CoV-2 infection among children is more prevalent than previously thought and emphasise the importance of seroprevalence studies to accurately estimate exposure.     

Effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infection and hospitalisation,Navarre, Spain,January to April 2021

COVID-19 vaccine effectiveness was evaluated in close contacts of cases diagnosed during January–April 2021. Among 20,961 contacts, 7,240 SARS-CoV-2 infections were confirmed, with 5,467 being symptomatic and 559 leading to hospitalisations. Non-brand-specific one and two dose vaccine effectiveness were respectively, 35% (95% confidence interval (CI): 25 to 44) and 66% (95% CI: 57 to 74) against infections, 42% (95% CI: 31 to 52) and 82% (95% CI: 74 to 88) against symptomatic infection, and 72% (95% CI: 47 to 85) and 95% (95% CI: 62 to 99) against COVID-19 hospitalisation. The second dose significantly increased effectiveness. Findings support continuing complete vaccination.     

Immunoglobulin (Ig)A seropositivity against SARS-CoV-2 in healthcare workers in Israel, 4 April to 13 July 2020: an observational study

IntroductionThe COVID-19 pandemic has put healthcare workers (HCW) at significant risk. Presence of antibodies can confirm prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.AimThis study investigates the prevalence of IgA and IgG antibodies against SARS-CoV-2 in HCW.MethodsPerformance of IgA and IgG antibody ELISA assays were initially evaluated in positive and negative SARS-CoV-2 serum samples. IgA and IgG antibodies against SARS-CoV-2 were measured in 428 asymptomatic HCW. We assessed the risk of two groups: HCW with high exposure risk outside work (HROW) residing in areas where COVID-19 was endemic (n = 162) and HCW with high exposure risk at work (HRAW) in a COVID-19 intensive care unit (ICU) (n = 97).ResultsSensitivities of 80% and 81.2% and specificities of 97.2% and 98% were observed for IgA and IgG antibodies, respectively. Of the 428 HCW, three were positive for IgG and 27 for IgA. Only 3/27 (11%) IgA-positive HCW had IgG antibodies compared with 50/62 (81%) in a group of previous SARS-CoV-2-PCR-positive individuals. Consecutive samples from IgA-positive HCW demonstrated IgA persistence 18–83 days in 12/20 samples and IgG seroconversion in 1/20 samples. IgA antibodies were present in 8.6% of HROW and 2% of HRAW.ConclusionsSARS-CoV-2 exposure may lead to asymptomatic transient IgA response without IgG seroconversion. The significance of these findings needs further study. Out of work exposure is a possible risk of SARS-CoV-2 infection in HCW and infection in HCW can be controlled if adequate protective equipment is implemented.     

Estimating the effect of mobility on SARS-CoV-2 transmission during the first and second wave of the COVID-19 epidemic,Switzerland, March to December 2020

IntroductionHuman mobility was considerably reduced during the COVID-19 pandemic. To support disease surveillance, it is important to understand the effect of mobility on transmission.AimWe compared the role of mobility during the first and second COVID-19 wave in Switzerland by studying the link between daily travel distances and the effective reproduction number (R_t ) of SARS-CoV-2.MethodsWe used aggregated mobile phone data from a representative panel survey of the Swiss population to measure human mobility. We estimated the effects of reductions in daily travel distance on R_t via a regression model. We compared mobility effects between the first (2 March–7 April 2020) and second wave (1 October–10 December 2020).ResultsDaily travel distances decreased by 73% in the first and by 44% in the second wave (relative to February 2020). For a 1% reduction in average daily travel distance, R_t was estimated to decline by 0.73% (95% credible interval (CrI): 0.34–1.03) in the first wave and by 1.04% (95% CrI: 0.66–1.42) in the second wave. The estimated mobility effects were similar in both waves for all modes of transport, travel purposes and sociodemographic subgroups but differed for movement radius.ConclusionMobility was associated with SARS-CoV-2 R_t during the first two epidemic waves in Switzerland. The relative effect of mobility was similar in both waves, but smaller mobility reductions in the second wave corresponded to smaller overall reductions in R_t . Mobility data from mobile phones have a continued potential to support real-time surveillance of COVID-19.     

SARS-CoV-2 testing in patients with low COVID-19 suspicion at admission to a tertiary care hospital,Stockholm, Sweden,March to September 2020

BackgroundUniversal SARS-CoV-2 testing at hospital admission has been proposed to prevent nosocomial transmission.AimTo investigate SARS-CoV-2 positivity in patients tested with low clinical COVID-19 suspicion at hospital admission.MethodsWe characterised a retrospective cohort of patients admitted to Karolinska University Hospital tested for SARS-CoV-2 by PCR from March to September 2020, supplemented with an in-depth chart review (16 March–12 April). We compared positivity rates in patients with and without clinical COVID-19 suspicion with Spearman’s rank correlation coefficient. We used multivariable logistic regression to identify factors associated with test positivity.ResultsFrom March to September 2020, 66.9% (24,245/36,249) admitted patient episodes were tested; of those, 61.2% (14,830/24,245) showed no clinical COVID-19 suspicion, and the positivity rate was 3.2% (469/14,830). There was a strong correlation of SARS-CoV-2 positivity in patients with low vs high COVID-19 suspicion (rho = 0.92; p < 0.001).From 16 March to 12 April, the positivity rate was 3.9% (58/1,482) in individuals with low COVID-19 suspicion, and 3.1% (35/1,114) in asymptomatic patients. Rates were higher in women (5.0%; 45/893) vs men (2.0%; 12/589; p = 0.003), but not significantly different if pregnant women were excluded (3.7% (21/566) vs 2.2% (12/589); p = 0.09). Factors associated with SARS-CoV-2 positivity were testing of pregnant women before delivery (odds ratio (OR): 2.6; 95% confidence interval (CI): 1.3–5.4) and isolated symptoms in adults (OR: 3.3; 95% CI: 1.8–6.3).ConclusionsThis study shows a relatively high SARS-CoV-2 positivity rate in patients with low COVID-19 suspicion upon hospital admission. Universal SARS-CoV-2 testing of pregnant women before delivery should be considered.     

SARS-CoV-2-host dynamics: Increased risk of adverse outcomes of COVID-19 in obesity

Background and aimThe pandemic of COVID-19 has put forward the public health system across countries to prepare themselves for the unprecedented outbreak of the present time. Recognition of the associated risks of morbidity and mortality becomes not only imperative but also fundamental to determine the prevention strategies as well as targeting the high-risk populations for appropriate therapies.MethodsWe reviewed, collated and analysed the online database i.e. Pubmed, Google scholar, Researchgate to highlight the demographic and mechanistic link between obesity and associated risks of severity in COVID-19.ResultsWe observed a changing dynamic in the reporting from the time of initial pandemic in China to currently reported research. While, initially body mass index (BMI) did not find a mention in the data, it is now clearly emerging that obesity is one of the profound risk factors for complications of COVID-19.ConclusionOur review will help clinicians and health policy makers in considering the importance of obesity in making the prevention and therapeutic strategies of COVID-19. An extra attention and precaution for patients with obesity in COVID-19 pandemic is recommended.     

External quality assessment of SARS-CoV-2 serology in European expert laboratories,April 2021

BackgroundCountries worldwide are focusing to mitigate the ongoing SARS-CoV-2 pandemic by employing public health measures. Laboratories have a key role in the control of SARS-CoV-2 transmission. Serology for SARS-CoV-2 is of critical importance to support diagnosis, define the epidemiological framework and evaluate immune responses to natural infection and vaccine administration.AimThe aim of this study was the assessment of the actual capability among laboratories involved in sero-epidemiological studies on COVID-19 in EU/EEA and EU enlargement countries to detect SARS-CoV-2 antibodies through an external quality assessment (EQA) based on proficiency testing.MethodsThe EQA panels were composed of eight different, pooled human serum samples (all collected in 2020 before the vaccine roll-out), addressing sensitivity and specificity of detection. The panels and two EU human SARS-CoV-2 serological standards were sent to 56 laboratories in 30 countries.ResultsThe overall performance of laboratories within this EQA indicated a robust ability to establish past SARS-CoV-2 infections via detection of anti-SARS-CoV-2 antibodies, with 53 of 55 laboratories using at least one test that characterised all EQA samples correctly. IgM-specific test methods provided most incorrect sample characterisations (24/208), while test methods detecting total immunoglobulin (0/119) and neutralising antibodies (2/230) performed the best. The semiquantitative assays used by the EQA participants also showed a robust performance in relation to the standards.ConclusionOur EQA showed a high capability across European reference laboratories for reliable diagnostics for SARS-CoV-2 antibody responses. Serological tests that provide robust and reliable detection of anti-SARS-CoV-2 antibodies are available.     

Risk reduction of hospitalisation and severe disease in vaccinated COVID-19 cases during the SARS-CoV-2 variant Omicron BA.1-predominant period,Navarre, Spain,January to March 2022

BackgroundAs COVID-19 vaccine effectiveness against SARS-CoV-2 infection was lower for cases of the Omicron vs the Delta variant, understanding the effect of vaccination in reducing risk of hospitalisation and severe disease among COVID-19 cases is crucial.AimTo evaluate risk reduction of hospitalisation and severe disease in vaccinated COVID-19 cases during the Omicron BA.1-predominant period in Navarre, Spain.MethodsA case-to-case comparison included COVID-19 epidemiological surveillance data in adults ≥ 18 years from 3 January–20 March 2022. COVID-19 vaccination status was compared between hospitalised and non-hospitalised cases, and between severe (intensive care unit admission or death) and non-severe cases using logistic regression models.ResultsAmong 58,952 COVID-19 cases, 565 (1.0%) were hospitalised and 156 (0.3%) were severe. The risk of hospitalisation was reduced within the first 6 months after full COVID-19 vaccination (complete primary series) (adjusted odds ratio (aOR): 0.06; 95% CI: 0.04–0.09) and after 6 months (aOR: 0.16; 95% CI: 0.12–0.21; p_comparison < 0.001), as well as after a booster dose (aOR: 0.06: 95% CI: 0.04–0.07). Similarly, the risk of severe disease was reduced (aOR: 0.13, 0.18, and 0.06, respectively). Compared with cases fully vaccinated 6 months or more before a positive test, those who had received a booster dose had lower risk of hospitalisation (aOR: 0.38; 95% CI: 0.28–0.52) and severe disease (aOR: 0.38; 95% CI: 0.21–0.68).ConclusionsFull COVID-19 vaccination greatly reduced the risk of hospitalisation and severe outcomes in COVID-19 cases with the Omicron variant, and a booster dose improved this effect in people aged over 65 years.